Natural antimicrobial peptides (AMPs) are among the first line of defense when organisms are under attack by bacterial pathogens. These host-defense peptides have shown broad-spectrum antimicrobial activity. (Brodgen, Nature Rev. Microbiol. 2005, 3, 238-250.) Because their production in the organism is much faster than that of specific antibodies, the AMPs are a vital component of innate immunity. AMPs are found in many species, including humans, animals, plants and invertebrates. Different from common antibiotics that target specific cell structures, AMPs use non-receptor interactions, including in many cases direct action against the bacteria's membranes. (Yang, et al, J. Am. Chem. Soc. 2007, 129, 12141.) The cells of the host organism are less affected. Thus, AMPs can selectively attack bacteria within a host organism. Bacteria could become immune to AMPs only when they change their entire membrane chemistry or other targets—thus resistance to AMPs is retarded as compared to other antibiotics. (Zasloff, Nature 2002, 415, 389-395.) Due to this promising feature, there has been increasing interest in synthetic mimics of antimicrobial peptides (SMAMPs). These include the SMAMPs made of α- and β-amino acids, peptoids, aromatic oligomers, and synthetic polymers. (Zasloff, Proc. Natl. Acad. Sci. USA 1987, 84, 5449; Castro, et al., Curr. Protein Peptide Sci. 2006, 7, 473; Chen, et al., J. Biol. Chem. 2005, 280, 12316; Won, et al., J. of Biol. Chem. 2004, 279, 14784; Hamuro, et al., J. Am. Chem. Soc. 1999, 121, 12200; Porter, et al., Nature 2000, 404, 565; Liu, et al., J. Am. Chem. Soc. 2001, 123, 7553; Epand, et al., Biochemistry 2004, 43, 9527; Patch, et al., J. Am. Chem. Soc. 2003, 125, 12092; Brouwer, et al., Peptides 2006, 27, 2585; Haynie, et al., Antimicrob. Agents Chemother. 1995, 39, 301; Tew, et al., Proc. Natl. Acad. Sci. USA 2002, 99, 5110; Liu, et al., Angew. Chem. Internat. Ed. 2004, 43, 1158; Tang, et al., Chem. Commun. 2005, 12, 1537; Kuroda, et al., J. Am. Chem. Soc. 2005, 127, 4128; Ilker, et al., J. Am. Chem. Soc. 2004, 126, 15870; Arnt, et al., J. Am. Chem. Soc. 2002, 124, 7664; Arnt, et al., Langmuir 2003, 19, 2404; Arm, et al., J. Polymer Sci. A, Polymer Chem. 2004, 42, 3860; Mowery, et al. J. Am. Chem. Soc. 2007, 129, 15474.)
One common feature of most AMPs is their positive charge and facial amphiphilicity. Regardless of the secondary structures, these peptides generally display one hydrophobic and one hydrophilic face along their backbone. (Brodgen, Nature Rev. Microbial. 2005, 3, 238-250; Boman, Immunol. Rev. 2000, 173, 5; Hancock, et al., Trends Biotech. 1998, 16, 82.) Due to positive charges in the hydrophilic part, AMPs bind preferentially to the anionic outer membranes of bacterial pathogens or other anionic targets including proteins and DNA. (Zasloff, Nature 2002, 415, 389-395; Yeaman, et al., Pharmacol. Rev. 2003, 55, 27.) In many cases, their facial amphiphilicity allows them to insert into the bacterial membrane and to locally change the membrane's lipid organization in such a way that trans-membrane pores are formed, although other mechanisms of action are also known. This interaction may lead to a breakdown of the membrane potential, the leaking of the cytoplasm and eventually the death of the pathogen cell. (Yount, et al., Biopolymers (Peptide Sci.) 2006, 84, 435.)
There is an unmet need for novel SMAMPs that possess desirable and tunable antimicrobial properties while at the same time are easy to prepare.